The magnitude of traumatic brain injury (TBI) related death and disability in this country supports investigating factors related to functional outcome attained after a TBI. The level of functional outcome that is attained by a TBI victim is highly variable, even when age, injury and care are similar, however the basis for this variability has never been adequately explained, and may hold the key to improving patient outcomes after a TBI. This study will take the approach that individual genetic variation may play a role in level of functional outcome attained after TBI and will specifically focus on individual mitochondrial genetics and mitochondrial energy production. A well-characterized cohort of TBI patients who have agreed to participate in a study on the genetics of recovery after TBI is available through the Brain Trauma Research Center (BTRC) at the University of Pittsburgh. The biological specimens and database that are viable for each subject will allow us to answer our hypotheses in an efficient and cost-effective manner. Venous blood sampling will allow us to investigate whether an individual's mitochondrial DNA (mtDNA) that is present constitutionally influences functional outcome attained after TBI. Cerebrospinal fluid (CSF) samples collected every 12 hours over the first five days after injury will allow us to investigate whether the mtDNA that is present in the environment of the brain injury influences functional outcome attained after TBI, including investigation of heteroplasmy. The CSF samples will also allow us to measure mitochondrial energy production in the environment of the brain injury over the first five days after injury to determine whether mitochondrial energy production influences functional outcome attained after TBI. The literature as well as our preliminary data supports this line of investigation. We have detected deletions in the mtDNA in a subset of these TBI patients and have correlated the deletion to reduced functional outcome and reduced mitochondrial energy production in these subjects. This line of investigation will help us better understand the role of mitochondria in functional outcome attained after TBI in humans and could have a significant clinical impact by helping clinicians to identify patients that require more aggressive therapies, provide more appropriate and earlier intervention, and develop targeted individualized therapy with the intention of improving patient outcomes after TBI.